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1

 Define the terms pathogen and commensal?

  • A pathogen is an organism which can cause an infection. 
  • Commensal is an organism which is part of a normal flora such as E.coli in the gut.

2

 Describe the features of clinical infection?

—Characterised by signs and symptoms:

  • —Inflammation
  • —Pain
  • —Pyrexia
  • —Increased white cell count
  • —Increased C reactive protein (CRP)

 

3

What is pathogenicity?

  • —The capacity of a micro-organism to cause an infection

4

What are the requirements of pathogenicity?

  1. Infectivity: Ability to become established
  2. Virulence: Ability to cause harmful effects once established

5

Give examples of infectivity?

 

  1. Attachment- E. coli

     2.Acid resistance

 

6

Virulence is conferred by virulence factors, what are they?

  • These are Genetically determined microbial components e.g 
  1. Invasiveness
  2. Toxin production
  3. Evasion of immune system

7

Examples of invasiveness?

  1. Streptococcus pyogenes (Group A streptococci)
  • Connective tissue breakdown
  • Fibrinolysis- Streptokinase

8

What are the 3 types of toxins?

  1. Exotoxins are released extracellularly by the micro-organism
  2. Enterotoxins are exotoxins which act on the GI tract
  3. Endotoxin is structurally part of the  Gram negative cell wall

9

Give an example of Enterotoxin?

 Cholera

—1.Vibrio cholerae

—Colonises small intestine

—2. Enterotoxin production

—Increases cAMP levels- Inhibits uptake of Na+ and Cl- ions

—3. Causes death by dehydration

—4. Treated by rehydration

 

10

Give an example of endotoxin?

  • —Component of the Gram-negative bacterial cell wall- —Lipopolysaccharide
  • —E. coli and other Gram-negative bacilli
  • —Induces severe uncontrolled host response - —Cytokine production

—

11

List the sites of viral entry?

  • Skin
  • Respiratory tract
  • Alimentary (digestive) tract
  • Urinogenital tract
  • Capillary and conjunctiva (the mucous membrane that covers the front of the eye and lines the inside of the eyelids.)

12

 Describe the features of acute viral infections with the use of examples?

  • Localised to affected sites of the body
  • Development of vireamia(the presence of viruses in the blood)  with widespread infection of tissues.
  • The  amount of virus spreads quickly as time increases until it reaches its maximum where the pateint shows symptoms and then the numbers decrease rapidly.
  • Influenza A virus infects cells of the respiratory tract and destroys respiratory epithelium.

13

How is generation of novel influenza viruses achived?

  • Antigenic DRIFT: Minor changes  (natural mutations) in the genes of flu viruses, occurs gradually over time to generate antigenic variants
  • Antigenic SHIFT: Abrupt major changes in virus antigenic structure

14

 Describe the features of enterovirus infection with the use of examples?

  • This infection mainly happens in the gastrointestinal tract. An example is poliomyelitis which causes the poliovirus.
  • The general principal is that the virus infection occurs in the gut, after this it can go in two paths.
  • The virus is either excreted in the feaces or there is the development of vireamia, and then the virus travels to the non or neural tissues and they both lead to paralysis

Note: Enteroviruses are a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine (enteric meaning intestinal).

15

 Describe how a virus can induce tumours with the use of examples?

  • Cervical sarcinoma. 
  • The virus infects the cell first, virus nucleic acid integrates into the cellular genome.
  • Viruses then cause changes in the cellulur gene expression which lead to uncontrolled multiplication and tumour formation.

16

Innate Immunity

  1. Skin, gastric acid, muco-ciliary escalator etc.
  2. Phagocytic cells - ingest foreign bodies
  • Polymorphs (acute - short lived)
  • Macrophages (chronic - long lived)
  • Fixed macrophages (liver, spleen, lymph nodes) of the mononuclear phagocytic system
  • Free macrophages in the tissues

17

Phagocytic cells

  1. Polymorphs (A polymorphonuclear leukocyte, they have granules in cytoplasm) - neutrophile, eosinophils, basophils

    2. Monocytes in blood mature into tissue macrophages 

Note: monocytes and lymphocytes are agranulocytes

18

Other white cells?

  1. —Lymphocytes are not phagocytic
  2. —Two different basic types:
  • —T cells (mature in thymus)
  • —B cells mature somewhere else

19

Mononuclear phagocytic system

  • Spleen clears blood (overwhelming Strep pneumoniae infection in splenectomy)
  • Liver clears entero-hepatic circulation
  • Regional lymph nodes drain peripheral sites

20

Opsonisation

  • —Organism coated with antibody or complement
  • —Phagocytic cell has receptors for both
  • —Efficiency of phagocytosis greatly improved
  • —Particularly important for capsulate bacteria (Strep pneumoniae, Haemophilus influenzae)

21

Acquired Immunity

  • —Specific response to antigen concerned
  • —Immunological memory created
  • —Humoral (antibody) and cellular (T cells)
  • —Each organism is a complex mixture of antigens
  • —Each antigen is (usually) a mixture of epitopes (part thats detected by WBC)

22

Antibody

  • Immunoglobulins (Ig) are the proteins with antibody activity - 5 classes
  1. Primary response (IgM): Good at fixing compliment and opsonization (kill bacteria)
  2. Secondary response (IgG): Good opsonizer (crosses placenta)
  3. Mucosal immunity (IgA): Protects mucosal surfaces, resistant to stomach acid (Neutralisation)
  4. Allergy and helminth infection (worm-like parasites) (IgE): can causes anaphylactic shock 
  5. IgD – No known Ab function

23

Lymphocytes

  • —B-lymphoctes differentiate into plasma cells when they recognise a specific epitope
  • —B-lymphocytes require T-cell help (CD4 T-cells)
  • —Monoclonal antibody from one clone of plasma cells has specificity for a single epitope
  • —Polyclonal antibody - multiple specificity
  • Epitope:  the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells.

24

Complement

  • Its a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen's plasma membrane.
  • It is part of the innate immune system, which is not adaptable and does not change over the course of an individual's lifetime.
  • It can be recruited and brought into action by antibodies generated by the adaptive immune system.
  • Complex cascade of 20 or so proteins - the most important are numbered C1 to C9.
  • —Combination of antibody (IgG or IgM only) and its specific antigen trigger the cascade of reactions
  • —Complement is said to be “fixed”

25

Humoral Immunity

  • —Mostly bacterial infection
  • —Extra-cellular
  • —Acute inflammation
  • —Neutrophilia

26

Cell mediated immunity

  • Macrophages “present” antigen and stimulate T-cells
  • Cytokines are produced and control the response
  • 2 main kinds of T cell
  • CD4 helper cells:

-Th1 - cell mediated immunity

-Th2 - control B cell antibody response

  • CD8 suppressor and cytotoxic cells

27

Superantigens

  • —Certain exotoxins of Strep pyogenes and Staph aureus
  • —Able to stimulate division of T cells in the absence of specific antigen
  • —Overwhelming cytokine production causes “toxic shock

28

Acute Virus Infections examples

 

Influenza A virus – respiratory infection

Enterovirus – enteric and neurological infections

29

Latent Virus Infections examples 

Herpes simplex virus – cold sores (type 1) and genital lesions (type 2)

  1. Primary infection of epithelial  cells.
  2. Virus migration to the ganglia.
  3. Virus remains latent in nucleus
  4. No Virus Replication.
  5. Stimuli (e.g. sunlight) reactivates virus.
  6. Virus migration to epithelial cells leading to virus replication.

30

Retrovirus replication pic